The Drug Abuse Basic Research Program in the department of pharmacology of The University of Michigan is composed of established investigators who have interrelated interests in problems related to drug abuse. Studies in the Monkey Colony will continue to be concerned with development of physical dependence to new analgesic agents, to morphine antagonists and to compounds which have mixed agonist-antagonist properties. These new drugs will also be tested for their ability to sustain self-administration by rhesus monkeys. The analysis of the reinforcing effect of these drugs will be enhanced by gathering information on important classes of related compounds and by studying the reinforcing effect of standard narcotics in other behaviorally significant situations. Biochemical studies will be concerned with he effects of drugs of abuse upon both the synthesis and the rate of turnover of such neurochemical transmitters as norepinephrine, dopamine and serotonin. New drugs will be evaluated in terms of their effects upon neurotransmitter synthesis and turnover. In addition, the role of neurotransmitters in the development of narcotic tolerance and dependence will be studied. The interaction of new narcotic drugs with opiate receptors and adenylate cyclase will be investigated. Cloned neurons and glia will be used as neurochemical models to study the differential effect in these two cell types of narcotic drugs on opiate receptors, membrane-bound enzymes and biogenic amine transport and metabolites.